Davidson J A, Perez A, Zhang J
Endocrine and Diabetes Associates of Texas, Dallas, TX 75230, USA.
Diabetes Obes Metab. 2006 Mar;8(2):164-74. doi: 10.1111/j.1463-1326.2005.00499.x.
To determine the effects of pioglitazone treatment combined with insulin on glucose and lipid metabolism in patients with type 2 diabetes.
In a multicentre, double-blind study, 690 patients [body mass index, 33.19 kg/m2 +/- 5.47; haemoglobin A1c (A1C), 9.78 +/- 1.51; mean duration, 12.9 years] with diabetes poorly controlled with a stable insulin dose (> 30 U/day for > or =30 days) were randomly allocated to pioglitazone 30 or 45 mg once daily for 24 weeks.
In the pioglitazone 30- and 45-mg groups, respectively, 71 and 70% of patients completed the study. At 24 weeks, statistically significant, dose-dependent mean decreases from baseline were seen in the pioglitazone 30- and 45-mg groups for A1C (-1.17 and -1.46%, respectively) and fasting plasma glucose (-31.9 and -45.8 mg/dl, respectively). Insulin dosage also decreased significantly (-4.5 and -7.3 U, respectively; p < or = 0.05) from baseline. Decreases in triglycerides [pioglitazone 45 mg: -5.9% (p < or = 0.05)], very low-density lipoprotein cholesterol [pioglitazone 45 mg: -6.2% (p < or = 0.05)] and free fatty acids [-0.94 (p < or = 0.05) and -2.13 (p < 0.0001) mg/dl, respectively] and increases in high-density lipoprotein cholesterol (9.7 and 13.0%, respectively; p < 0.0001) also were observed from baseline. Small but significant increases in total and low-density lipoprotein cholesterol (p < 0.01) from baseline were observed. Mean weight gain was 2.9 and 3.4 kg in the respective groups; lower limb oedema was reported in 13 and 12% of patients, respectively. The incidences of oedema, weight gain and heart failure were not higher than anticipated in this population. No evidence of hepatotoxicity or clinically significant elevations in liver function test parameters was seen.
In patients with poorly controlled type 2 diabetes, addition of pioglitazone to insulin significantly improved glycaemic control, had a positive effect on important components of the lipid profile in a dose-dependent manner and was generally well tolerated.
确定吡格列酮联合胰岛素治疗对2型糖尿病患者糖脂代谢的影响。
在一项多中心、双盲研究中，690例糖尿病患者[体重指数为33.19 kg/m²±5.47；糖化血红蛋白（A1C）为9.78±1.51；平均病程为12.9年]，使用稳定胰岛素剂量（≥30 U/天且持续≥30天）血糖控制不佳，被随机分配至每日一次服用30或45 mg吡格列酮，疗程24周。
在吡格列酮30 mg组和45 mg组中，分别有71%和70%的患者完成了研究。在24周时，吡格列酮30 mg组和45 mg组的A1C（分别降低-1.17%和-1.46%）及空腹血糖（分别降低-31.9和-45.8 mg/dl）较基线水平有统计学意义的剂量依赖性平均降低。胰岛素剂量也较基线水平显著降低（分别降低-4.5和-7.3 U；p≤0.05）。甘油三酯[吡格列酮45 mg：-5.9%（p≤0.05）]、极低密度脂蛋白胆固醇[吡格列酮45 mg：-6.2%（p≤0.05）]和游离脂肪酸（分别降低-0.94（p≤0.05）和-2.13（p<0.0001）mg/dl）较基线水平降低，高密度脂蛋白胆固醇较基线水平升高（分别升高9.7%和13.0%；p<0.0001）。总胆固醇和低密度脂蛋白胆固醇较基线水平有小幅度但显著的升高（p<0.01）。各组平均体重增加分别为2.9 kg和3.4 kg；分别有13%和12%的患者报告有下肢水肿。水肿、体重增加和心力衰竭的发生率不高于该人群的预期。未发现肝毒性证据或肝功能检查参数有临床显著升高。
在2型糖尿病控制不佳的患者中，胰岛素联合吡格列酮可显著改善血糖控制，对血脂谱的重要成分有剂量依赖性的积极影响，且总体耐受性良好。
